Acute kidney injury (AKI) is a serious condition which can occur post-operatively, for example as a complication of cardiac surgery or kidney transplant, as a side effect from the in vivo introduction of diagnostic agents, for example, X-ray contrast agents, or nephrotoxic therapeutic agents, and the like, and/or in connection with other medical conditions, for example, diabetes, septicemia, hemorrhagic shock, and the like. As an example, acute kidney injury may occur in up to 30% of all patients undergoing cardiac surgery and is associated with a high mortality, a more complicated hospital course, dialysis dependency, diminished quality of life, and a higher risk for infectious complications. While the introduction of therapy in early stages of acute kidney failure has been shown to reduce the mortality rate and/or shorten treatment regimens, it has often been difficult to detect acute kidney failure in early stages.
In current clinical practice, the standard diagnosis of AKI is called RIFLE (Rise, Injury, Failure, Loss, End-stage renal disease) which is based on either the elevation of serum creatinine or urine output reduction. Serum creatinine is a reliable marker of general kidney function but it is an unreliable and delayed indicator during acute changes in kidney function. Fortunately, several promising novel biomarkers, including HNL/NGAL (hereafter referred to as NGAL), kidney injury molecule-1, cystatin C, and IL-18, have been discovered.
A great deal of attention has been directed to the use of NGAL protein as a marker for acute kidney injury. NGAL is a glycoprotein and was originally identified as a neutrophil specific granule component and a member of the lipocalin family of proteins. The protein was shown to exist both as a 25-kDa monomer and a 45-kDa disulfide-linked homodimer, and it may also be covalently complexed with neutrophil gelatinase (also known as matrix metalloproteinase 9, MMP-9) via an intermolecular disulphide bridge as a 135-kDa heterodimeric form. NGAL was first described as HNL as a specific marker of neutrophil activity in vivo and in vitro by Xu et al, Journal of Immunological Methods, 171:245-252 (1994), and for use as a diagnostic marker for inflammation by Venge, U.S. Pat. No. 6,136,526, which is incorporated herein by reference.
More recently, Devarajan et al, U.S. Patent Publications Nos. 2004/0219603 A1 and 2005/0272101 A1, disclose use of NGAL as a biomarker for renal tubular cell injury and other renal disease and injury. BioBorto Diagnostics, Gentofte, Denmark, recently offered an “NGAL ELISA Kit”, for early diagnosis of acute renal failure, as well as mouse monoclonal anti-human NGAL antibody and mouse monoclonal anti-rat NGAL antibody. Additionally, Dent et al, Critical Care, 11(6):R127 (2007), describe the Triage® NGAL device from Biosite Inc., San Diego, Calif., employing an NGAL-specific monoclonal antibody conjugated to a fluorescent nanoparticle, for use in measuring NGAL as a biomarker of acute kidney injury.
However, further improvements in detecting and/or monitoring acute kidney injury are desired.